Tuberculoid leprosy: An in vivo microvascular evaluation of cutaneous lesions.

Tuberculoid leprosy (TT) is characterized by cutaneous lesions called plaques. Although microvascular ultrastructure of TT patients' skin is well-documented, little is known about functional aspects of their microcirculation. We aimed, for the first time, to evaluate, in vivo, the microcirculation of TT cutaneous lesions. Seven TT patients, males, under treatment were included in the study. The spectral analysis of frequency components of flowmotion (endothelial, sympathetic, myogenic, cardiac and respiratory) was performed using laser Doppler flowmetry (LDF). Endothelial dependent and independent vasodilatations were assessed by LDF associated to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis, respectively. Vessel density (VD), perfused vessel density (PVD), proportion of perfused vessels (PPV%), microvascular flow index (MFI) and flow heterogeneity index (FHI), reflecting tissue perfusion and oxygenation, were evaluated through sidestream dark field (SDF) imaging. All microvascular analysis were performed in TT lesions and in healthy skin in the contralateral limb of the same patient, used as control skin. VD, PVD and PPV% and MFI were significantly lower in the cutaneous lesion compared to contralateral healthy skin. The contribution of different frequency components of flowmotion, endothelial dependent and independent vasodilatations and FHI were not statistically different between control skin and cutaneous lesion. Our results suggest that TT cutaneous lesions have a significant impairment of tissue perfusion, which may aggravate peripheral nerve degeneration caused by Mycobacterium leprae infection.

Histopathology of the lepromatous skin biopsy.

The histopathology of lepromatous skin varies according to the cell-mediated immunity of the host against Mycobacterium leprae. In tuberculoid and borderline tuberculoid leprosy, epithelioid noncaseating granulomas predominate, and acid-fast bacilli (AFB) are absent or only rarely present. In borderline lepromatous and lepromatous leprosy, the infiltrate is composed of macrophages with a vacuolar cytoplasm, lymphocytes, and plasma cells. AFB are numerous. Edema inside and outside the epithelioid granulomas, together with the appearance of large giant cells, are the main features of type 1 reactions. A conspicuous neutrophilic infiltrate in the subcutis with or without vasculitis is found in erythema nodosum leprosum. The main histopathologic features of leprosy and its particular forms are discussed in this review.

Clinical aspects of leprosy.

Leprosy is a chronic, infectious disease caused by Mycobacterium leprae. It mainly affects the peripheral nervous system, skin, and certain other tissues such as the reticulo-endothelial system, bones and joints, mucous membranes, eyes, testes, muscles, and adrenals. Leprosy clinical presentation varies from few to widespread lesions. In most patients, early leprosy presents as macular and hypopigmented lesions. This initial clinical presentation is known as indeterminate leprosy and occurs in individuals who have not developed cell-mediated immunity against M. leprae yet. The number of lesions depends on the genetically determined cellular immunity of the patient. Individuals presenting a vigorous cellular immune response and limited humoral immune responses to M. leprae, usually present few skin lesions. Without treatment, those patients tend to evolve into the polar tuberculoid or borderline tuberculoid form of leprosy. Due to the inability to mount an effective cellular-mediated response to M. leprae and the consequent hematogenous spread of the bacilli, some patients may present with numerous and symmetrically distributed hypochromic lesions. Without treatment these patients evolve to a nonresistant form of leprosy, polar lepromatous.

Primary neural leprosy: systematic review.

The authors proposed a systematic review on the current concepts of primary neural leprosy by consulting the following online databases: MEDLINE, Lilacs/SciELO, and Embase. Selected studies were classified based on the degree of recommendation and levels of scientific evidence according to the "Oxford Centre for Evidence-based Medicine". The following aspects were reviewed: cutaneous clinical and laboratorial investigations, i.e. skin clinical exam, smears, and biopsy, and Mitsuda's reaction; neurological investigation (anamnesis, electromyography and nerve biopsy); serological investigation and molecular testing, i.e. serological testing for the detection of the phenolic glycolipid 1 (PGL-I) and the polymerase chain reaction (PCR); and treatment (classification criteria for the definition of specific treatment, steroid treatment, and cure criteria).

Primary neural leprosy: systematic review / Hanseníase neural primária: revisão sistemática

The authors proposed a systematic review on the current concepts of primary neural leprosy by consulting the following online databases: MEDLINE, Lilacs/SciELO, and Embase. Selected studies were classified based on the degree of recommendation and levels of scientific evidence according to the “Oxford Centre for Evidence-based Medicine”. The following aspects were reviewed: cutaneous clinical and laboratorial investigations, i.e. skin clinical exam, smears, and biopsy, and Mitsuda's reaction; neurological investigation (anamnesis, electromyography and nerve biopsy); serological investigation and molecular testing, i.e. serological testing for the detection of the phenolic glycolipid 1 (PGL-I) and the polymerase chain reaction (PCR); and treatment (classification criteria for the definition of specific treatment, steroid treatment, and cure criteria).

Os autores propuseram-se a realizar uma revisão sistemática em conceitos atuais sobre a hanseníase neural primária, consultando as seguintes bases bibliográficas on-line: MEDLINE, Lilacs/SciELO e Embase. Os estudos selecionados foram classificados conforme o grau de recomendação e o nível de evidência científica de acordo com o “Oxford Centre for Evidence-based Medicine”. Os seguintes temas foram revisados: investigações clínica e laboratorial cutâneas, ou seja, exame, esfregaço e biópsia de pele e reação de Mitsuda; investigação neurológica (anamnese, eletroneuromiografia e biópsia de nervo); investigação sorológica e testes moleculares, ou seja, testes sorológicos para detecção de um glicolipídio fenólico e reação de cadeia de polimerase (PCR) e tratamento (critérios de classificação para definição de tratamento específico, tratamento com esteroides e critérios de cura).

Experimental leprosy: a model of epithelioid cell granuloma.

An animal model of granulomatous hypersensitivity has been developed, which reproduces some features of the pathologies of important chronic granulomatous disorders, including tuberculosis, tuberculoid leprosy, sarcoidosis, berylliosis, Crohn's disease, and sensitivity to zirconium. The lesions consist of focal collections of epithelioid cells surrounded by lymphocytes to form tubercles. The epithelioid cell has a secretory function and is not phagocytic. Plasmacytoid dendritic cells are precursors of epithelioid cells, which are therefore part of the innate immune system. Subplasmalemmal linear densities are also present in these cells. This autoimmune model has been induced in rabbits using a non-myelin sensory peripheral antigen to reproduce the features of tuberculoid leprosy. The antigen is probably present only in human tissue. A granuloma antigen, which is tissue specific similar to that in peripheral nerves, could be present in sarcoidosis and Crohn's disease. In multiple sclerosis, mononuclear cells in the brain parenchyma are not phagocytic and are therefore similar to epithelioid cells. The induction of tolerance leading to the development of a vaccine to prevent the lesions in multiple sclerosis, sarcoidosis, and Crohn's disease is possible after purification of the granuloma antigen.

Mutilating acral ulcers: the spectrum of differential diagnosis.

Prominent acral mutilating ulcers can be present in sensorimotor neuropathies. Although diabetes mellitus is the most common cause of neuropathic ulcers, these skin lesions may manifest in nondiabetic neuropathies. The dermatologic abnormalities may even precede the onset of typical neuropathic symptoms, leading to diagnostic confusion. Therefore, a broad differential diagnosis of neurological and systemic disorders should be considered when evaluating patients who have acral skin ulcerations. We report 3 cases of mutilating ulcers associated with nondiabetic neuropathies. The first case is a woman with multiple ulcerations on her forearm, hands, and toes. Her nerve biopsy revealed neuropathy with multiple congophilic deposits consistent with amyloid neuropathy. The second case is a woman with necrotic painless ulcer on her heel. Nerve biopsy in this patient revealed features suggestive of vasculitic neuropathy. The third case is a man with multiple ulcers on his extremities. A sural nerve biopsy in this patient was consistent with leprous neuropathy.

Proprioceptive loss in leprous neuropathy: a study of 19 patients.

BACKGROUND: Leprosy presents commonly with mononeuritis multiplex, affecting mainly the exteroceptive sensations. Neuropathy with a significant afferent large fiber element is considered to be an uncommon manifestation of leprous neuropathy. AIMS: To evaluate the clinical and neurophysiologic aspects of a subset of patients with leprous neuropathy having clinical proprioceptive loss. SETTINGS AND DESIGN: Prospective study of patients with a diagnosis of peripheral neuropathy secondary to leprosy having proprioceptive loss. MATERIALS AND METHODS: Consecutive patients seen during a two-year period (2004 and 2005) diagnosed to have leprous neuropathy with proprioceptive abnormalities on clinical examination were included. The diagnosis of leprosy was achieved by clinical features along with positive skin biopsy, split skin smears or nerve biopsy. Their clinical and electrophysiological characteristics were studied. STATISTICAL METHODS: The results were analyzed using Chi-Square test. Values less than 0.05 were considered to be statistically significant . RESULTS AND CONCLUSIONS: We observed predominance (68.42%) of multibacillary of leprosy. Symmetrical neuropathies outnumbered mononeuritis multiplex (12:7). The pan sensory neuropathy had a mean duration of 24.32 months, but sometimes appeared early in the course of the disease. Areflexia and electrophysiological evidence of proximal affection was common, reflecting proximal spread of neuropathic process. Such patients have a higher incidence of developing deformities and ulcerations and they represent a vulnerable subset of patients with leprosy.

Estudo terapêutico comparando a associação de rifampicina, ofloxacina e minociclina com a associação rifampicina, clofazimina e dapsona em pacientes com hanseniase multibacilar / Therapeutical study comparing the association of rifampin, ofloxacine e minocycline with a association rifampin, clofazimine e dapsone in patients with bacillus leprosy

O presente trabalho comparou dois esquemas terapêuticos em pacientes com hanseniase multibacilar. O grupo l, que recebeu o tratamento convencional (PQT-MB), foi denominado grupo de controle. O grupo 2, denominado de grupo teste, recebeu a associação de rifampicina 600mg, mais ofloxacina 400mg, mais minociclina 100mg (ROM), administrado sob supervisão, uma vez por mês. A duração total do tratamento nos dois grupos foi de dois anos. Na avaliação inicial foram realizados: exame clinico, baciloscopio e histologico. A baciloscopia e a biopsia foram repetidas no final do primeiro ano e novamente no final do segundo ano de tratamento. A avaliação clinica foi realizada mensalmente por ocasião da administração da dose supervisionada. No grupo 1 foram avaliados 14 pacientes. O indice baciloscopio (IB) antes do tratamento variou de 2 a 4,8. No grupo 2 foram estudados 12 pacientes. O IB antes do tratamento nesse grupo variou de m1,6 a 4,8. Ambos os grupos apresentavam lesões cutâneas que os caracterizavam como pertencentes ao pólo vichoviano. Histologicamente apresentavam quadro de hanseniase virchoviana ativa, exceto um paciente do grupo 2. Ao final do primeiro ano de tratamento estavam todos clinicamente melhorados, o indice baciloscopio diminuido e com quadro histologico em regressão. Essa tendencia de melhora se mantinha e na avaliação do finanl do segundo ano todos estavam clinicamente, baciloscopidamente e histologicamente ainda melhores. A análise estatistica dos parametros, baciloscopio e histologico, mostrou que não houve diferença estatisticamente significativa entre os grupos estudados, sendo, portanto os dois esquemas equivalentes. A ocorrência de reação tipo 2(eritema nodoso hansenico-ENH) foi igual nos dois grupos. no primeiro grupo 1, todos apresentaram pigmentação cutânea devido a clofazimina. Os resultados, portanto, demonstraram que o esquema com administração mensal de rifampicina, mais ofloxacina, mais minociclina tem eficácia e segurança equivalenteao esquema convencional. Além disso, tem a vantagem de não acarretar pigmentação cutânes, ser totalmente supervisionado, podendo ser utilizado como esquema alternativo.

Manifestaçoes fonoaudiologicas em um grupo de doentes de Hanseniase / Manifestations fonoaudiologicas in a group of patients from leprosy

A Hansenise, doença cronica infecto-contagiosa e de nofificaçao compulsoria, e causada pelo bacilo de Hansen (Mycobacterium leprae), e pode apresentar multiplas lesoes em qualquer local do corpo...

A case of isolated tuberculoid leprosy of antebrachial medial cutaneous nerve.

Leprosy is an infectious disease of prevalence still high in endemic areas in Brazil. The neurological presentation depends on the involved nerve and is usually associated with skin lesions and the formation of multiple abscesses. We present a case of isolated tuberculoid leprosy, discuss the occurrence, the differential diagnosis and the treatment of this rare presentation and reaffirm the importance of considering leprosy in the differential diagnosis of patients with polyneuropathy or nerve enlargement with no skin lesions.

Importância do reconhecimento clínico da hanseníase / Importance of clinical recognition of hanseniase

Neste artigo é realizada uma discussão sobre a hanseníase, relevante doença infecciosa no mundo, com importância marcante nas áreas tropicais. Procurou-se enfatizar os aspectos clínicos e imunopatogênicos, como forma de se proporcionar um melhor panorama do estado atual do problema

A study of leprosy reactions in a tertiary hospital in Delhi.

A retrospective study of 531 leprosy patients was undertaken to study the profile of reactions in the post Multi-Drug-Therapy period in a tertiary hospital in Delhi. BT was the most common group. The prevalence of reactions was found to be 8.09% for the Type 1 and 4.70% for the Type 2 reactions for a male:female ratio of 2.2. The Type 1 reaction was most frequently observed in the BB group followed by BL, BT and LL groups respectively. More than half of the patients had reactions at the time of presentation. In only 39.8% of the patients did reaction follow Multi-Drug-Therapy. In 4.5% of the patients with Type 1 reactions (T1R), concomitant infections were noted. The most common presentation of T1R was cutaneous lesions (74.41%) followed by cutaneous lesions and neuritis (53.6%), neuritis alone (12.1%), and only edema of hands and feet (7.31%) respectively. The Type 2 reactions (T2R) presented chiefly as papulo-nodular (92%) lesions followed by pustulonecrotic (8%) lesions. Associated neuritis was found in 40% and periosteitis and iritis in 8% and 4%, respectively. In 8.6% of the patients with T2R, precipitating factors could be observed. The prevalence of deformities in patients with reaction was 25%, and was more common in females. Deformities were observed in 23.25% of the T1R patients and 28% of the T2R patients.

An evaluation of clinical and histopathological status in paucibacillary leprosy patients after completion of sixed duration therapy

The presente study was carried out involving 25 patients with paucibacillary leprosy who attended the outpatient department of dermatology of Father Muller's Medical College Hospital during the period January 2001 to March 2002. All the patients were examined clinically and histopathologically at the beginning and at the end of six months of MDT and relevant data recorded. Clinicopathological correlation with histopathological classification before MDT was 72% and 68% at the end of MDT in our study. At the end of treatment 4 (16%) cases were clinically active and 8 (32%) were histopathologically active. The study showed that active cases were siginificantly reduced as a result of MDT, both clinically and histopatologically. The histopathological activity that outlasts MDT may be due to the bacillary fragments that persist; but clincial activity coupled with histopathological activity seen in 2 patients at the end of 6 months of MDT was possibly an indicator of relapse and these patients and similar others need to be follewed up for a longer duration. Is this study, resolution of granuloma and clinical activity after completion of MDT were assessed

Use of genetic profiling in leprosy to discriminate clinical forms of the disease.

Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.

Use of genetic profiling in leprosy to discriminate clinical forms of the disease

Leprosy presents as a clinical and immunological spectrum of disease. With the use of gene expression profiling, we observed that a distinction in gene expression correlates with and accurately classifies the clinical form of the disease. Genes belonging to the leukocyte immunoglobulin-like receptor (LIR) family were significantly up-regulated in lesions of lepromatous patients suffering from the disseminated form of the infection. In functional studies, LIR-7 suppressed innate host defense mechanisms by shifting monocyte production from interleukin-12 toward interleukin-10 and by blocking antimicrobial activity triggered by Toll-like receptors. Gene expression profiles may be useful in defining clinical forms of disease and providing insights into the regulation of immune responses to pathogens.